Very low birth weight infants who require total parenteral nutrition (TPN) due to enteral feeding intolerance have a limited capacity to utilize energy in the form of glucose and long-chain triglycerides (LCT). Achieving sufficient caloric intake for growth and a positive nitrogen balance is one of the big challenges in the care of these patients. In the proposed research, the incorporation of medium-chain triglycerides (MCT) as a readily available alternative source of energy into the TPN regimen will be explored. MCT-containing lipid emulsions are being studied in adults. No studies in premature infants have been reported in the U.S., yet their potential benefit may be greatest in this patient population. The scientific hypotheses of this proposal are: (1) MCT have a more pronounced ketogenic effect than LCT. This could be beneficial for brain development, but could also cause toxicity; and (2) MCT decrease the availability of free carnitine, resulting in an accumulation of short- and medium-chain acyl-coenzyme A and impairment of energy metabolism if exogenous carnitine is not supplied. The proposed experimental approaches are novel: The first hypothesis will be tested by determining rates of ketone body turnover and clearance in premature infants 26-32 weeks of gestation during infusion of a mixture of MCT and LCT (MCT/LCT) in comparison with a pure LCT emulsion, using stable isotope technology. The second hypothesis will be tested by measuring parameters of carnitine metabolism and evaluating the effect of L-carnitine supplementation on ketone body kinetics during MCT/LCT infusion. The long term goal is to determine whether the addition of MCT and L-carnitine to TPN will improve the nutrition of premature infants during a critical period of their lives.